Magnetic Resonance Imaging Relaxation Time Research Articles

Detection of early metaphyseal changes in a piglet model of Legg-Calvé-Perthes disease using quantitative mapping of MRI relaxation times.

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder characterized by ischemic injury to the epiphysis of the femoral head, but changes to the metaphysis have also been implicated in its pathogenesis. Quantitative magnetic resonance imaging (MRI) relaxation time mapping techniques are potentially useful to detect injury in LCPD, but studies to date have focused on the epiphysis. The purpose of this study was to assess whether T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times can detect early metaphyseal changes in an LCPD piglet model. Complete epiphyseal ischemia of one femoral head was surgically induced and confirmed using contrast-enhanced MRI in n = 10 6-week-old piglets; the contralateral side was unoperated. The bilateral hips were imaged 1 week after surgery in vivo at 3T MRI using relaxation time mapping and contrast-enhanced MRI. Relaxation times and thicknesses of the metaphyseal primary and secondary spongiosa were measured and compared between the ischemic and contralateral-control femoral heads using paired t-tests. In the ischemic femoral heads, T2 relaxation times were significantly increased in the primary spongiosa (6.7 ± 9.8 ms, p = 0.029), and T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times were significantly decreased in the secondary spongiosa (respectively: -13.3 ± 9.3 ms, p = 0.013; -32 ± 23 ms, p < 0.001; -43 ± 41 ms, p = 0.009; and -39 ± 13 ms, p < 0.001). The secondary spongiosa thickness was also significantly decreased in the ischemic femoral heads (p < 0.001). In conclusion, T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques can detect early changes in the metaphysis following ischemic injury to the epiphysis of the femoral head in a piglet model of LCPD.

Quantitative MRI Analysis of Patellofemoral Joint Cartilage Health 2 Years After Anterior Cruciate Ligament Reconstruction and Lateral Extra-Articular Tenodesis

Background: The addition of an iliotibial band–based lateral extra-articular tenodesis (LET) to anterior cruciate ligament (ACL) reconstruction (ACLR) has been shown to reduce failure rates. However, there are concerns as to the potential overconstraint of tibiofemoral kinematics that may increase the risk of cartilage degradation. To date, no clinical study has investigated the effect of LET on patellofemoral joint articular cartilage health. Hypothesis: It was hypothesized that at 2 years postoperatively, (1) the addition of LET at the time of ACLR would have no effect on cartilage health on magnetic resonance imaging (MRI), and (2) higher cartilage relaxation values would be associated with worse patient-reported and functional outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: A subset of patients from the STABILITY 1 randomized controlled trial were included. All patients underwent primary ACLR with a hamstring autograft. Patients were randomized to either LET augmentation or not. Cartilage status in the patellofemoral joint between the ACLR group and ACLR+LET group was compared using 2-year postoperative quantitative MRI and the ACL osteoarthritis scores of both the surgical and the contralateral nonsurgical knees. Objective functional outcomes and patient-reported outcome measures (PROMs) were attained. Results: A total of 92 patients (43 patients in the ACLR group; mean age, 18.9 ± 3.2 years; 60.5% female; and 49 patients in the ACLR+LET group; mean age, 18.7 ± 3.2 years, 63.3% female) were included. No significant differences were seen in the mean values (ms) for adjusted T1ρ/T2 relaxation times in the medial patella (47.8/42.2 vs 47.3/43.2), central patella (45.5/42.5 vs 44.1/42.7), lateral patella (48.2/43.5 vs 47.3/43.0), medial trochlea (54.7/50.9 vs 56.4/50.9), central trochlea (53.3/51.1 vs 53.1/52.0), and lateral trochlea (54.9/52.1 vs 53.9/52.6) between the ACLR and ACLR+LET groups. No difference in overall ACL osteoarthritis scores was observed (P = .99). An increase in medial patellar T2 relaxation times was associated with a decreasing International Knee Documentation Committee score (P = .046), Knee injury and Osteoarthritis Outcome Score (KOOS) Symptoms subscale score (P = .01), and total KOOS (P = .01). Conclusion: There was no statistical difference in patellofemoral cartilage health between knees 2 years after primary ACLR with hamstring tendon autograft with or without LET. Statistically significant correlations were found between quantitative MRI relaxation times, functional outcome scores, and PROMs; however, the correlations were weak and the clinical significance is unknown. Registration: NCT02018354 (ClinicalTrials.gov identifier).

Comparison of Algorithms to Compute Relaxation Time Maps in Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a valuable diagnostic tool that provides detailed information about the structure and function of tissues in the human body. In particular, measuring relaxation times, such as T1 and T2, can provide important insights into the composition and properties of different tissues. Accurate relaxation time mapping is therefore critical for clinical diagnosis and treatment planning, as it can help to identify and characterize pathological conditions, monitor disease progression, and guide interventions. However, the computation of relaxation time maps in MRI is a complex and challenging task that requires sophisticated mathematical algorithms. Thus, there is a need for robust and accurate algorithms that can reliably extract the desired information from MRI data. This article compares the performance of the Reduced Dimension Nonlinear Least Squares (RD-NLS) algorithm versus several widely used algorithms to compute relaxation times in MRI, such as Levenberg-Marquardt and Nelder-Mead. RD-NLS simplifies the search space for the optimum fit by leveraging the partial linear relationship between signal intensity and model parameters. The comparison was performed on several datasets and signal models, resulting in T1 and T2 maps. The algorithms were evaluated based on their fit error, with the RD-NLS algorithm showing a lower error than other fit-ting algorithms. The improvement was particularly notable in T1 maps, with less of a difference in T2 maps. Additionally, the average T1 values computed with different algorithms differed by up to 14 ms, indicating the importance of algorithm selection. These results suggest that the RD-NLS algorithm outperforms other commonly used algorithms for computing relaxation times in MRI.

Gait Variability Structure Linked to Worse Cartilage Composition Post-ACL Reconstruction.

Aberrant gait variability has been observed after anterior cruciate ligament reconstruction (ACLR), yet it remains unknown if gait variability is associated with early changes in cartilage composition linked to osteoarthritis development. Our purpose was to determine the association between femoral articular cartilage T1ρ magnetic resonance imaging relaxation times and gait variability. T1ρ magnetic resonance imaging and gait kinematics were collected in 22 ACLR participants (13 women; 21 ± 4 yr old; 7.52 ± 1.43 months post-ACLR). Femoral articular cartilage from the ACLR and uninjured limbs were segmented into anterior, central, and posterior regions from the weight-bearing portions of the medial and lateral condyles. Mean T1ρ relaxation times were extracted from each region and interlimb ratios (ILR) were calculated (i.e., ACLR/uninjured limb). Greater T1ρ ILR values were interpreted as less proteoglycan density (worse cartilage composition) in the injured limb compared with the uninjured limb. Knee kinematics were collected at a self-selected comfortable walking speed on a treadmill with an eight-camera three-dimensional motion capture system. Frontal and sagittal plane kinematics were extracted, and sample entropy was used to calculate kinematic variability structure (KV structure ). Pearson's product-moment correlations were conducted to determine the associations between T1ρ and KV structure variables. Lesser frontal plane KV structure was associated with greater mean T1ρ ILR in the anterior lateral ( r = - 0.44, P = 0.04) and anterior medial condyles ( r = - 0.47, P = 0 .03). Lesser sagittal plane KV structure was associated with greater mean T1ρ ILR in the anterior lateral condyle ( r = - 0.47, P = 0.03). The association between less KV structure and worse femoral articular cartilage proteoglycan density suggests a link between less variable knee kinematics and deleterious changes joint tissue changes. The findings suggest that less knee kinematic variability structure is a mechanism linking aberrant gait to early osteoarthritis development.

Interlimb differences in T1ρ MRI relaxation times linked with symptomatic knee osteoarthritis following anterior cruciate ligament reconstruction

BackgroundLower proteoglycan density, as estimated by greater T1ρ magnetic resonance imaging (MRI) relaxation times, may be an indicator of early osteoarthritis development. We examined associations between femoral cartilage inter-limb T1ρ MRI relaxation time ratios and clinically relevant knee symptoms at 12 months following anterior crucial ligament reconstruction (ACLR). MethodsTwenty-nine individuals completed the Knee Osteoarthritis Outcome Score (KOOS) and underwent MRI 12 months following ACLR for this cross-sectional study. Participants were categorized as symptomatic or asymptomatic for clinically relevant knee symptoms consistent with osteoarthritis based on a standard KOOS classification. T1ρ MRI relaxation times were segmented in the weightbearing regions of lateral and medial femoral condyle (LFC and MFC). Inter-limb T1ρ MRI relaxation time ratios were calculated by normalizing the ACLR to the uninjured knee. T-tests were used to compare LFC and MFC interlimb T1ρ relaxation time ratios between individuals with and without knee symptoms. A Receiver Operating Characteristic (ROC) Curve analysis was used to determine a critical inter-limb T1ρ relaxation time ratio identifying symptomatic patients. Odds ratios (OR) and 95% confidence intervals (CI) estimated the association between the critical value and clinically relevant knee symptoms. ResultsSymptomatic individuals had significantly higher LFC inter-limb T1ρ MRI relaxation time ratios compared to asymptomatic individuals (p = 0.04). Individuals with an LFC inter-limb T1ρ MRI relaxation time ratio >1.11 were more likely to have symptoms (OR 8.5; 95%CI = 1.25–57.93). ConclusionIndividuals with greater inter-limb LFC T1ρ MRI relaxation time ratios 12 months post-ACLR may be more likely to exhibit symptoms consistent with knee OA.

Preparation and evaluation of bismuth sulfide and magnetite‐based theranostic nanohybrid as drug carrier and dual MRI/CT contrast agent

Due to the increased incidence and population growth that has been leading to growing number of cases worldwide, early diagnosis and treatment of cancer is crucial. Low density cancer tissue cannot be diagnosed before progressing toward a metastatic stage. Thus, theranostic systems play a significant role in assisting timely diagnosis and treatment. The combination of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents in a single probe is of high importance and necessity, where individual strengths of each approach can be merged while shortcomings of each modality could be compensated. With this motivation, we have developed and synthesized Bi2S3@BSA‐Fe3O4 nanoparticles as a dual MRI/CT contrast agent and carrier of curcumin (CUR) as natural anticancer drug. The nanoparticles shortened both the longitudinal (T1) and transverse (T2), MRI relaxation times, with a more distinct effect on producing negative contrast (T2) images with a relaxivity (r2) of 54.73 mM−1 s−1. The magnetite/bismuth hybrid nanoparticle also was capable of increasing CT image contrast. Further, in vitro cytotoxicity assay showed high biocompatibility of the synthesized nanoparticles. Furthermore, in vitro cytotoxicity assay on cancer cells showed high anticancer activity of the synthesized nanoparticles.

More Regular Gait Patterns Associate With Worse Femoral Cartilage Composition Following Anterior Cruciate Ligament Reconstruction

Individuals with anterior cruciate ligament reconstruction (ACLR) exhibit more regular gait patterns, resulting in more rigid movements compared to controls. Aberrant joint loading post-ACLR is linked to worse T1ρ magnetic resonance imaging (MRI) relaxation times, an outcome associated with osteoarthritis development. Yet, it remains unknown if knee movement regularity during gait associates with knee cartilage composition in individuals with ACLR. PURPOSE: Determine the association between femoral articular cartilage T1ρ MRI relaxation times and knee joint movement regularity during gait. METHODS: T1ρ MRI and gait kinematics were collected in 20 participants with ACLR (13 Females; 21 ± 4 years old; 8 ± 1 months post-ACLR). Femoral articular cartilage from the ACLR and uninjured limbs was segmented into anterior, central, and posterior regions from the weightbearing portions of the medial and lateral condyles. Mean T1ρ relaxation times were extracted from the cartilage in each region and interlimb ratios were calculated (i.e., ACLR / uninjured limb). Greater interlimb T1ρ ratios were interpreted as lesser proteoglycan density (worse cartilage composition) in the injured limb compared to the uninjured limb. Knee kinematics were collected at a self-selected gait speed on a treadmill with an 8-camera 3D motion capture system. Frontal and sagittal plane knee kinematics were extracted, and sample entropy was used to calculate the degree of movement regularity (i.e., lower values reflect more regularity). Pearson’s product-moment correlations were conducted to determine the association between T1ρ and movement regularity variables. RESULTS: Greater frontal plane knee movement regularity associated with greater mean T1ρ interlimb ratios in the anterior portions of the lateral (r = -0.44, p = .04) and medial condyles (r = -0.47, p = .03). Greater sagittal plane kinematic regularity associated with greater mean T1ρ interlimb ratios in the anterior portion of the lateral condyle (r = -0.47, p = .03). CONCLUSION: Greater movement regularity was associated with less femoral articular cartilage proteoglycan density which is linked to early osteoarthritis development. We hypothesize that greater movement regularity contributes to less adaptable gait and more concentrated cartilage loading.

Worse Tibiofemoral Cartilage Composition Is Associated with Insufficient Gait Kinetics After ACL Reconstruction.

Greater articular cartilage T1ρ magnetic resonance imaging relaxation times indicate less proteoglycan density and are linked to posttraumatic osteoarthritis development after anterior cruciate ligament reconstruction (ACLR). Although changes in T1ρ relaxation times are associated with gait biomechanics, it is unclear if excessive or insufficient knee joint loading is linked to greater T1ρ relaxation times 12 months post-ACLR. The purpose of this study was to compare external knee adduction (KAM) and flexion (KFM) moments in individuals after ACLR with high versus low tibiofemoral T1ρ relaxation profiles and uninjured controls. Gait biomechanics were collected in 26 uninjured controls (50% females; age, 22 ± 4 yr; body mass index, 23.9 ± 2.8 kg·m -2 ) and 26 individuals after ACLR (50% females; age, 22 ± 4 yr; body mass index, 24.2 ± 3.5 kg·m -2 ) at 6 and 12 months post-ACLR. ACLR-T1ρ High ( n = 9) and ACLR-T1ρ Low ( n = 17) groups were created based on 12-month post-ACLR T1ρ relaxation times using a k-means cluster analysis. Functional analyses of variance were used to compare KAM and KFM. ACLR-T1ρ High exhibited lesser KAM than ACLR-T1ρ Low and uninjured controls 6 months post-ACLR. ACLR-T1ρ Low exhibited greater KAM than uninjured controls 6 and 12 months post-ACLR. KAM increased in ACLR-T1ρ High and decreased in ACLR-T1ρ Low between 6 and 12 months, both groups becoming more similar to uninjured controls. There were scant differences in KFM between ACLR-T1ρ High and ACLR-T1ρ Low 6 or 12 months post-ACLR, but both groups demonstrated lesser KFM compared with uninjured controls. Associations between worse T1ρ profiles and increases in KAM may be driven by the normalization of KAM in individuals who initially exhibit insufficient KAM 6 months post-ACLR.

Loading during Midstance of Gait Is Associated with Magnetic Resonance Imaging of Cartilage Composition Following Anterior Cruciate Ligament Reconstruction.

ObjectiveA complex association exists between aberrant gait biomechanics and posttraumatic knee osteoarthritis (PTOA) development. Previous research has primarily focused on the link between peak loading during the loading phase of stance and joint tissue changes following anterior cruciate ligament reconstruction (ACLR). However, the associations between loading and cartilage composition at other portions of stance, including midstance and late stance, is unclear. The objective of this study was to explore associations between vertical ground reaction force (vGRF) at each 1% increment of stance phase and tibiofemoral articular cartilage magnetic resonance imaging (MRI) T1ρ relaxation times following ACLR.DesignTwenty-three individuals (47.82% female, 22.1 ±4.1 years old) with unilateral ACLR participated in a gait assessment and T1ρ MRI collection at 12.25 ± 0.61 months post-ACLR. T1ρ relaxation times were calculated for the articular cartilage of the weightbearing medial and lateral femoral (MFC, LFC) and tibial (MTC, LTC) condyles. Separate bivariate, Pearson product moment correlation coefficients (r) were used to estimate strength of associations between T1ρ MRI relaxation times in the medial and lateral tibiofemoral articular cartilage with vGRF across the entire stance phase.ResultsGreater vGRF during midstance (46%-56% of stance phase) was associated with greater T1ρ MRI relaxation times in the MFC (r ranging between 0.43 and 0.46).ConclusionsBiomechanical gait profiles that include greater vGRF during midstance are associated with MRI estimates of lesser proteoglycan density in the MFC. Inability to unload the ACLR limb during midstance may be linked to joint tissue changes associated with PTOA development.

Changes in magnetic resonance imaging relaxation time on postmortem magnetic resonance imaging of formalin-fixed human normal heart tissue

BackgroundPostmortem magnetic resonance imaging (MRI) has been used to investigate the cause of death, but due to time constraints, it is not widely applied to the heart. Therefore, MRI analysis of the heart after formalin fixation was previously performed. However, the changes in MRI signal values based on the fixation time of formalin were not investigated. The objective was to investigate changes over time in the T1- and T2-values of MRI signals in normal areas of hearts removed during autopsy, hearts subsequently fixed in formalin, and heart specimens sliced for the preparation of pathological specimens.MethodsThe study subjects were 21 autopsy cases in our hospital between May 26, 2019 and February 16, 2020 whose hearts were removed and scanned by MRI. The male:female ratio was 14:7, and their ages at death ranged from 9 to 92 years (mean age 65.0 ± 19.7 years). Postmortem (PM)-MRI was conducted with a 0.3-Tesla (0.3-T) scanner containing a permanent magnet. A 4-channel QD head coil was used as the receiver coil. Scans were performed immediately after removal, post-formalin fixation, and after slicing; 7 cases were scanned at all three time points.ResultsThe T1- and T2-values were calculated from the MRI signals of each sample organ at each scanning stage. Specimens were sliced from removed organs after formalin fixation, and the changes in T1- and T2-values over time were graphed to obtain an approximate curve. The median T1-values at each measurement time point tended to decrease from immediately after removal. The T2-values showed the same tendency to decrease, but this tendency was more pronounced for the T1-values.ConclusionMRI signal changes in images of heart specimens were investigated. Formalin fixation shortened both T1- and T2-values over time, and approximation formulae were derived to show these decreases over time. The shortening of T1- and T2-values can be understood as commensurate with the reduction in the water content (water molecules) of the formalin-fixed heart.

Association of Jump-Landing Biomechanics With Tibiofemoral Articular Cartilage Composition 12 Months After ACL Reconstruction.

Background:Excessively high joint loading during dynamic movements may negatively influence articular cartilage health and contribute to the development of posttraumatic osteoarthritis after anterior cruciate ligament reconstruction (ACLR). Little is known regarding the link between aberrant jump-landing biomechanics and articular cartilage health after ACLR.Purpose/Hypothesis:The purpose of this study was to determine the associations between jump-landing biomechanics and tibiofemoral articular cartilage composition measured using T1ρ magnetic resonance imaging (MRI) relaxation times 12 months postoperatively. We hypothesized that individuals who demonstrate alterations in jump-landing biomechanics, commonly observed after ACLR, would have longer T1ρ MRI relaxation times (longer T1ρ relaxation times associated with less proteoglycan density).Study Design:Cross-sectional study; Level of evidence, 3.Methods:A total of 27 individuals with unilateral ACLR participated in this cross-sectional study. Jump-landing biomechanics (peak vertical ground-reaction force [vGRF], peak internal knee extension moment [KEM], peak internal knee adduction moment [KAM]) and T1ρ MRI were collected 12 months postoperatively. Mean T1ρ relaxation times for the entire weightbearing medial femoral condyle, lateral femoral condyle (global LFC), medial tibial condyle, and lateral tibial condyle (global LTC) were calculated bilaterally. Global regions of interest were further subsectioned into posterior, central, and anterior regions of interest. All T1ρ relaxation times in the ACLR limb were normalized to the uninjured contralateral limb. Linear regressions were used to determine associations between T1ρ relaxation times and biomechanics after accounting for meniscal/chondral injury.Results:Lower ACLR limb KEM was associated with longer T1ρ relaxation times for the global LTC (ΔR 2 = 0.24; P = .02), posterior LTC (ΔR 2 = 0.21; P = .03), and anterior LTC (ΔR 2 = 0.18; P = .04). Greater ACLR limb peak vGRF was associated with longer T1ρ relaxation times for the global LFC (ΔR 2 = 0.20; P = .02) and central LFC (ΔR 2 = 0.15; P = .05). Peak KAM was not associated with T1ρ outcomes.Conclusion:At 12 months postoperatively, lower peak KEM and greater peak vGRF during jump landing were related to longer T1ρ relaxation times, suggesting worse articular cartilage composition.

Reproducibility of T1 relaxation times in diagnostic MRI: A phantom study

T1 mapping is crucial for many quantitative magnetic resonance imaging (MRI) procedures. However, studies have reported wide T1 variations, both in vivo and in vitro. Since clinical decisions depend on T1 relaxation times, evaluating the factors affecting their reproducibility is necessary. Available studies are limited in that they do not provide a comparative perspective on the variation of T1 relaxation times as a function of relevant parameters, such as pulse sequence type, magnetic field strength and how their interplay with the scanner model affects the resulting T1 values. To address these gaps, we imaged two phantoms modelling T1 of different samples at 1.5 T and 3.0 T using fast and slow inversion recovery (IR) sequences. The results show that T1 relaxation times from 3.0 T scanners are accurate and reproducible in terms of the expected reference values and when compared between different scanner models. Similarly, T1 values measured with the two pulse sequences were similar for all 3.0 T scanners. On the contrary, 1.5 T scanners exhibited larger discrepancies in the measured T1 compared with the reference values. In addition, 1.5 T scanners displayed less reproducibility in T1 relaxation time measurements across different 1.5 T scanners, and pulse sequences.

Loading during midstance of gait is associated with tibiofemoral articular cartilage composition following anterior cruciate ligament reconstruction

Loading during midstance of gait is associated with tibiofemoral articular cartilage composition following anterior cruciate ligament reconstruction

Talar and Subtalar T1ρ Relaxation Times in Limbs with and without Chronic Ankle Instability.

ObjectiveThe primary aim was to determine differences in talocrural and subtalar joint (STJ) articular cartilage composition, using T1ρ magnetic resonance imaging (MRI) relaxation times, between limbs in individuals with unilateral chronic ankle instability (CAI) and compare with an uninjured control. Our secondary purpose was to determine the association between talocrural and STJ composition in limbs with and without CAI.DesignT1ρ MRI relaxation times were collected on 15 CAI (11 females, 21.13 ± 1.81 years, body mass index [BMI] = 23.96 ± 2.74 kg/m2) and 15 uninjured control individuals (11 females, 21.07 ± 2.55 years, BMI = 24.59 ± 3.44 kg/m2). Talocrural cartilage was segmented manually to identify the overall talar dome. The SJT cartilage was segmented manually to identify the anterior, medial, and posterior regions of interest consistent with STJ anatomical articulations. For each segmented area, a T1ρ relaxation time mean and variability value was calculated. Greater T1ρ relaxation times were interpreted as decreased proteoglycan content.ResultsIndividuals with CAI demonstrated a higher involved limb talocrural T1ρ mean and variability relative to their contralateral limb (P < 0.05) and the healthy control limb (P < 0.05). The CAI-involved limb also had a higher posterior STJ T1ρ mean relative to the healthy control limb (P < 0.05). In healthy controls (P < 0.05), but not the CAI-involved or contralateral limbs (p>0.05), talocrural and posterior STJ composition measures were positively associated.ConclusionsIndividuals with CAI have lower proteoglycan content in both the talocrural and posterior STJ in their involved limbs relative to the contralateral and a healthy control limb. Cartilage composition findings may be consistent with the early development of posttraumatic osteoarthritis.

Development of phantom materials with independently adjustable CT- and MR-contrast at 0.35, 1.5 and 3 T

Quality assurance in magnetic resonance (MR)-guided radiotherapy lacks anthropomorphic phantoms that represent tissue-equivalent imaging contrast in both computed tomography (CT) and MR imaging. In this study, we developed phantom materials with individually adjustable CT value as well as - and -relaxation times in MR imaging at three different magnetic field strengths. Additionally, their experimental stopping power ratio (SPR) for carbon ions was compared with predictions based on single- and dual-energy CT. Ni-DTPA doped agarose gels were used for individual adjustment of and at and 3.0 T. The CT value was varied by adding potassium chloride (KCl). By multiple linear regression, equations for the determination of agarose, Ni-DTPA and KCl concentrations for given and CT values were derived and employed to produce nine specific soft tissue samples. Experimental and CT values of these soft tissue samples were compared with predictions and additionally, carbon ion SPR obtained by range measurements were compared with predictions based on single- and dual-energy CT. The measured CT value, and of the produced soft tissue samples agreed very well with predictions based on the derived equations with mean deviations of less than While single-energy CT overestimates the measured SPR of the soft tissue samples, the dual-energy CT-based predictions showed a mean SPR deviation of only To conclude, anthropomorphic phantom materials with independently adjustable CT values as well as and relaxation times at three different magnetic field strengths were developed. The derived equations describe the material specific relaxation times and the CT value in dependence on agarose, Ni-DTPA and KCl concentrations as well as the chemical composition of the materials based on given and CT value. Dual-energy CT allows accurate prediction of the carbon ion range in these materials.

MR-labelled liposomes and focused ultrasound for spatiotemporally controlled drug release in triple negative breast cancers in mice

Rationale: Image-guided, triggerable, drug delivery systems allow for precisely placed and highly localised anti-cancer treatment. They contain labels for spatial mapping and tissue uptake tracking, providing key location and timing information for the application of an external stimulus to trigger drug release. High Intensity Focused Ultrasound (HIFU or FUS) is a non-invasive approach for treating small tissue volumes and is particularly effective at inducing drug release from thermosensitive nanocarriers. Here, we present a novel MR-imageable thermosensitive liposome (iTSL) for drug delivery to triple-negative breast cancers (TNBC).Methods: A macrocyclic gadolinium-based Magnetic Resonance Imaging (MRI) contrast agent was covalently linked to a lipid. This was incorporated at 30 mol% into the lipid bilayer of a thermosensitive liposome that was also encapsulating doxorubicin. The resulting iTSL-DOX formulation was assessed for physical and chemical properties, storage stability, leakage of gadolinium or doxorubicin, and thermal- or FUS-induced drug release. Its effect on MRI relaxation time was tested in phantoms. Mice with tumours were used for studies to assess both tumour distribution and contrast enhancement over time. A lipid-conjugated near-infrared fluorescence (NIRF) probe was also included in the liposome to facilitate the real time monitoring of iTSL distribution and drug release in tumours by NIRF bioimaging. TNBC (MDA-MB-231) tumour-bearing mice were then used to demonstrate the efficacy at retarding tumour growth and increasing survival.Results: iTSL-DOX provided rapid FUS-induced drug release that was dependent on the acoustic power applied. It was otherwise found to be stable, with minimum leakage of drug and gadolinium into buffers or under challenging conditions. In contrast to the usually suggested longer FUS treatment we identified that brief (~3 min) FUS significantly enhanced iTSL-DOX uptake to a targeted tumour and triggered near-total release of encapsulated doxorubicin, causing significant growth inhibition in the TNBC mouse model. A distinct reduction in the tumours' average T1 relaxation times was attributed to the iTSL accumulation.Conclusions: We demonstrate that tracking iTSL in tumours using MRI assists the application of FUS for precise drug release and therapy.

Multi-parametric MRI of kidney disease progression for autosomal recessive polycystic kidney disease: mouse model and initial patient results.

Background:Autosomal recessive polycystic kidney disease (ARPKD) is a rare but potentially lethal genetic disorder typically characterized by diffuse renal microcysts. Clinical trials for patients with ARPKD are not currently possible due to the absence of sensitive measures of ARPKD kidney disease progression and/or therapeutic efficacy.Methods:In this study, animal and human MRI scanners were used to obtain quantitative kidney T1 and T2 relaxation time maps for both excised kidneys from bpk and wild type (WT) mice as well as for a pediatric patient with ARPKD and a healthy adult volunteer.Results:Mean kidney T1 and T2 relaxation times showed significant increases with age (p<0.05) as well as significant increases in comparison to WT mice (p<2 × 10−10). Significant or nearly significant linear correlations were observed for mean kidney T1 (p=0.030) and T2 (p=0.054) as a function of total kidney volume, respectively. Initial MRF assessments in a patient with ARPKD showed visible increases in both kidney T1 and T2 in comparison to the healthy volunteer.Conclusions:These preclinical and initial clinical MRI studies suggest that renal T1 and T2 relaxometry may provide an additional outcome measure to assess cystic kidney disease progression in patients with ARPKD.

P010 Measurement of colonic mucosal content of biologics with the use of magnetic resonance imaging (MRI): A pilot study in patients with ulcerative colitis

Abstract Background Anti-tumour necrosis factor antagonists (infliximab) as well as other molecules with different modes of action, including anti-integrin agents (vedolizumab), are currently used in patients with ulcerative colitis (UC Numerous studies have demonstrated a positive correlation between serum biologic drug concentrations and favourable therapeutic outcomes, whereas low or undetectable drug concentrations can lead to treatment failure. However, despite immunological issues, lack of and or loss of response may also be attributed to drug pharmacokinetics, of which penetration to the target tissue (colon wall) may play a crucial role Methods We used MRI to perform biochemical analyses of infliximab, adalimumab and vedolizumab concentrations testing the hypothesis that MRI relaxation time can be used to track antibodies in both mucosal biopsy samples and serum. All MR scans were performed with an Optima MR360 from General Electric Healthcare. To determine spin–lattice (T1) and spin–spin (T2) relaxation times, the Fast Spin Echo (FSE) sequence was used. Results The measured values of T1 relaxation times for infliximab, adalimumab, and vedolizumab were 2227 ± 35 ms, 2000 ± 22 ms and 1288 ± 15 ms, respectively. The obtained T2 relaxation times were 130 ± 11 ms, 90 ± 5, and 75 ± 10 ms, respectively. A decrease of both T1 and T2 values of 15 ± 3% are observed in serum from patients with ulcerative colitis. The values of infliximab and adalimumab were similar; the values of vedolizumab measurements in serum were about 50% lower. We find primary evidence that in T1 and T2 decreased in serum samples with ulcerative colitis and increase with the administration of infliximab, adalimumab and vedolizumab drugs. Samples of healthy tissue have T1 and T2 in the range of 2700 ± 5 ms and 150 ms ± 5 ms, respectively. A 30% decrease in T1 and T2 are observed for samples with ulcerative colitis. In this pilot study, we observed that values of T1 and T2 for tissues and serum that contain infliximab and adalimumab are similar, but vedolizumab shows a difference of about 30% when compared with infliximab and adalimumab. Conclusion MRI is an excellent method for quantitative and qualitative measurements of drug content in tissues and biological fluids. This is an innovative use of magnetic resonance imaging to develop a methodology for imaging of drugs that act as contrast agents via interaction with water in serum and tissue.

The utility of MRI for measuring hematocrit in fetal anemia

Doppler ultrasound measurements of the peak systolic velocity of the middle cerebral artery can be used to noninvasively diagnose fetal anemia but are less precise following fetal blood transfusion and in late gestation. We have previously demonstrated the feasibility of estimating fetal hematocrit invitro using magnetic resonance imaging relaxation times. Here we report the use of magnetic resonance imaging as a noninvasive tool to accurately detect fetal anemia invivo. This study has 2 objectives: (1) to determine the feasibility and accuracy of magnetic resonance imaging in estimating hematocrit in anemic fetuses and (2) to compare magnetic resonance imaging and middle cerebral artery Doppler in detecting moderate to severe fetal anemia. Fetuses undergoing fetal blood sampling or transfusion underwent magnetic resonance imaging examinations prior to and following their procedures at 1.5 Tesla (Siemens Avanto). A modified Look-Locker inversion pulse sequence and T2 preparation sequence were applied for T1 and T2 mapping of the intrahepatic umbilical vein. Estimated fetal hematocrit was calculated using a combination of T1 and T2 values and compared with conventional hematocrit obtained from fetal blood samples and middle cerebral artery Doppler measurements. Twenty-three fetuses were assessed during 33 magnetic resonance imaging scans. The mean absolute difference between the laboratory and magnetic resonance imaging-estimated hematocrit was 0.06± 0.05 with a correlation of 0.77 (P < .001) determined by a multilevel, mixed-effects model adjusting for the repeated measurements from the same participants, multiple gestation pregnancies, and the scan type (ie, before or after transfusion scan). Bland-Altman analysis revealed a systematic bias of -0.03 between the magnetic resonance imaging and fetal blood sampling measurements. Magnetic resonance imaging and middle cerebral artery Doppler had similar sensitivities of approximately 90% to detect moderate to severe anemia. However, magnetic resonance imaging had a higher specificity (93% [13/14], 95% confidence interval, 66-100%) than Doppler (71% [10/14], 95% confidence interval, 42-92%). Moderate to severe fetal anemia can be detected noninvasively by magnetic resonance imaging with high sensitivity and specificity. Our results suggest an adjunct role for magnetic resonance imaging in fetuses with suspected anemia, particularly following previous transfusion and in late gestation.

Characterizing mechanical and medical imaging properties of polyvinyl chloride-based tissue-mimicking materials.

Polyvinyl chloride (PVC) is a commonly used tissue‐mimicking material (TMM) for phantom construction using 3D printing technology. PVC‐based TMMs consist of a mixture of PVC powder and dioctyl terephthalate as a softener. In order to allow the clinical use of a PVC‐based phantom use across CT and magnetic resonance imaging (MRI) imaging platforms, we evaluated the mechanical and physical imaging characteristics of ten PVC samples. The samples were made with different PVC‐softener ratios to optimize phantom bioequivalence with physiologic human tissue. Phantom imaging characteristics, including computed tomography (CT) number, MRI relaxation time, and mechanical properties (e.g., Poisson’s ratio and elastic modulus) were quantified. CT number varied over a range of approximately −10 to 110 HU. The relaxation times of the T1‐weighted and T2‐weighted images were 206.81 ± 17.50 and 20.22 ± 5.74 ms, respectively. Tensile testing was performed to evaluate mechanical properties on the three PVC samples that were closest to human tissue. The elastic moduli for these samples ranged 7.000–12.376 MPa, and Poisson’s ratios were 0.604–0.644. After physical and imaging characterization of the various PVC‐based phantoms, we successfully produced a bioequivalent phantom compatible with multimodal imaging platforms for machine calibration and image optimization/benchmarking. By combining PVC with 3D printing technologies, it is possible to construct imaging phantoms simulating human anatomies with tissue equivalency.